This Physician/Scientist Award is designed to provide a rigorous and thorough scientific training in preparation for a career in academic medicine with intensive basic science research commitment. It combines the superb academic atmosphere at the Whitehead Institute, Massachusetts Institute of Technology, the Harvard Medical School and the Massachusetts General Hospital (MGH). The Phase One sponsor, Dr. David Baltimore, has an impressive enthusiasm for the nurture and training of young physician/ scientists. Phase One will involve an intensive research experience at the Whitehead Institute. At the same time, graduate level course work in molecular genetics, molecular virology and immunology will be conducted at Harvard, M.I.T. and the Marine Biological Laboratory at Woods Hole. In Dr. David Baltimore's laboratory, the research will focus on the understanding of Human immunodeficiency Virus (HIV) replication in the monocyte/macrophage. The extremely complex nature of HIV replication will be investigated using gel retardation assays and DNA protection assays to study cell-specific factors involved in directing the transcription of HIV proteins. An important cell-derived factor, NF Kappa B, which has been shown to be involved in HIV replication in T cell lines, will be studied in the monocyte/macrophage. We will also investigate whether there are genetic differences in a cell tropic versus monocyte/macrophage tropic HIV strains. Restriction enzyme analysis, cloning and nucleotide sequencing of specific HIV isolates with differing cell tropism will be performed to examine whether there exist specific genetic differences in HIV strains within the long terminal repeat and/or the envelope glycoprotein region. A rigorous understanding of HIV production in the monocyte/ macrophage will be key in understanding a variety of the pathogenetic mechanisms of this virus. During this time, the candidate will become familiar with a number of important and generalizable molecular virologic techniques.